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Background@#Human adenovirus (HAdV) is a common cause of acute respiratory disease (ARD) and has raised significant concerns within the Korean military. Here, we conducted a comprehensive epidemiological analysis of HAdV-associated ARD by evaluating its prevalence, clinical outcomes, and prognosis. @*Methods@#We reviewed data from multiple sources, including the New Defense Medical Information System, Defense Medical Statistical Information System, Ministry of National Defense, Army Headquarters, Navy Headquarters, Air Force Headquarters, and Armed Forces Medical Command. We analyzed data of patients who underwent polymerase chain reaction (PCR) testing for respiratory viruses between January 2013 and July 2022 in all 14 Korean military hospitals. The analysis included the PCR test results, demographic characteristics, health care utilization, and prognosis including types of treatments received, incidence of pneumonia, and mortality. @*Results@#Among the 23,830 individuals who underwent PCR testing at Korean military hospitals, 44.78% (10,670 cases) tested positive for respiratory viruses. Across all military types and ranks, HAdV was the most prevalent virus, with a total of 8,580 patients diagnosed, among HAdV, influenza virus, human metapneumovirus, human parainfluenza virus, and human respiratory syncytial virus. HAdV-infected patients exhibited higher rates of healthcare use compared to non-HAdV-infected patients, including a greater number of emergency visits (1.04 vs. 1.02) and outpatient visits (1.31 vs. 1.27), longer hospitalizations (8.14 days vs. 6.84 days), and extended stays in the intensive care unit (5.21 days vs. 3.38 days).Furthermore, HAdV-infected patients had a higher proportion of pneumonia cases (65.79%vs. 48.33%) and greater likelihood of receiving advanced treatments such as high flow nasal cannula or continuous renal replacement therapy. @*Conclusion@#Our findings indicate that HAdV posed a significant public health concern within the Korean military prior to the coronavirus disease 2019 (COVID-19) pandemic. Given the potential for a resurgence of outbreaks in the post-COVID-19 era, proactive measures, such as education, environmental improvements, and the development of HAdV vaccines, are crucial for effectively preventing future outbreaks.
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Background/Aims@#The effectiveness of remdesivir treatment in reducing mortality and the requirement for mechanical ventilation (MV) remains uncertain, as randomized controlled trials (RCTs) have produced conflicting results. @*Methods@#We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and other data resources to find RCTs published prior to April 10, 2023. The selection of studies, assessment of risk of bias, and meta-analysis were conducted according to PRISMA guidelines. The primary outcomes were all-cause mortality and the need to initiate MV. @*Results@#A total of 5,068 articles were screened, from eight RCTs comprising 11,945 patients. The meta-analysis found that, compared to standard care or placebo, remdesivir treatment provided no significant all-cause mortality benefit (pooled risk ratio [RR], 0.93; 95% confidence interval [CI], 0.85–1.02; 8 studies; high certainty evidence), while subgroup analyses revealed a trend towards reduced mortality among patients requiring oxygen but not MV (pooled RR, 0.88; 95% CI, 0.77–1.00; 6 studies; I2 = 4%). The need to initiate MV (pooled RR, 0.74; 95% CI, 0.59–0.94; 7 studies; moderate certainty evidence) in remdesivir-treated patients was also reduced compared to controls. Remdesivir significantly increased clinical improvement and discharge and significantly reduced serious adverse events. @*Conclusions@#In this systematic review and meta-analysis of RCTs, it was found that remdesivir treatment did not show a substantial decrease in the risk of mortality. However, it was linked to a reduction in the necessity for additional ventilatory support, suggesting remdesivir could be beneficial for COVID-19 patients, particularly those who are not on MV.
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Tixagevimab/cilgavimab is a monoclonal antibody used to prevent coronavirus disease 2019 among immunocompromised hosts and maintained neutralizing activity against early omicron variants. Omicron BN.1 became a dominant circulating strain in Korea early 2023, but its susceptibility to tixagevimab/cilgavimab is unclear. We conducted plaque reduction neutralization test (PRNT) against BN.1 in a prospective cohort (14 patients and 30 specimens). BN.1 PRNT was conducted for one- and three-months after tixagevimab/ cilgavimab administration and the average PRNT ND 50 of each point was lower than the positive cut-off value of 20 (12.9 ± 4.5 and 13.2 ± 4.2, respectively, P = 0.825). In the paired analyses, tixagevimab/cilgavimab-administered sera could not actively neutralize BN.1 (PRNT ND 50 11.5 ± 2.9, P = 0.001), compared with the reserved activity against BA.5 (ND 50 310.5 ± 180.4). Unlike virus-like particle assay, tixagevimab/cilgavimab was not active against BN.1 in neutralizing assay, and would not be effective in the present predominance of BA.2.75 sublineages.
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Background@#In Korea, during the early phase of the coronavirus disease 2019 (COVID-19) pandemic, we responded to the uncertainty of treatments under various conditions, consistently playing catch up with the speed of evidence updates. Therefore, there was high demand for national-level evidence-based clinical practice guidelines for clinicians in a timely manner. We developed evidence-based and updated living recommendations for clinicians through a transparent development process and multidisciplinary expert collaboration. @*Methods@#The National Evidence-based Healthcare Collaborating Agency (NECA) and the Korean Academy of Medical Sciences (KAMS) collaborated to develop trustworthy Korean living guidelines. The NECA-supported methodological sections and 8 professional medical societies of the KAMS worked with clinical experts, and 31 clinicians were involved annually. We developed a total of 35 clinical questions, including medications, respiratory/critical care, pediatric care, emergency care, diagnostic tests, and radiological examinations. @*Results@#An evidence-based search for treatments began in March 2021 and monthly updates were performed. It was expanded to other areas, and the search interval was organized by a steering committee owing to priority changes. Evidence synthesis and recommendation review was performed by researchers, and living recommendations were updated within 3–4 months. @*Conclusion@#We provided timely recommendations on living schemes and disseminated them to the public, policymakers and various stakeholders using webpages and social media.Although the output was successful, there were some limitations. The rigor of development issues, urgent timelines for public dissemination, education for new developers, and spread of several new COVID-19 variants have worked as barriers. Therefore, we must prepare systematic processes and funding for future pandemics.
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As nucleocapsid protein of severe acute respiratory syndrome coronavirus 2 is immunogenic but not targeted in vaccines, it could be useful in distinguishing natural infection from vaccination. We aimed to investigate the clinical utility of sero-immunological responses against the nucleocapsid protein. Nucleocapsid antibody immunoassay study with 302 coronavirus disease 2019 (COVID-19) patients showed lower titers in immunocompromised patients (P < 0.001), higher titers in higher severity (P = 0.031), and different seroconversion rates and titers according to variants of concern. Longitudinal evaluation of nucleocapsid antibodies using 513 samples from 291 COVID-19 patients revealed that it could persist up to 556 days from symptom onset. Interferon gamma release assay against the nucleocapsid protein showed poor response, precluding the deduction of a cut-off for the nucleocapsid protein. In conclusion, nucleocapsid antibody provides instructive clues about the immunogenicity of nucleocapsid proteins by different seroconversion rates and titers according to the severity of infection, host immune status, and different variants of concern.
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The coronavirus disease 2019 pandemic has brought significant changes to infectious disease management globally. This study explored changes in clinical microbiological testing trends and their implications for infectious disease incidence and medical utilization during the pandemic. We collected nationwide claims for monthly clinical microbiology tests from January 2018 to March 2022 using the National Health Insurance Service database. Seasonal autoregressive integrated moving average models were employed to make predictions for each disease based on the baseline period (January 2018 to January 2020). The results showed a significant decrease in general bacterial and fungal cultures, respiratory infectious diseaserelated, and inflammatory markers, while the representatives of tests for vector-borne diseases, healthcare-associated infections, and chronic viral infections remained stable.The study highlights the potential of clinical microbiological testing trends as an additional surveillance tool and offers implications for future infectious disease management and surveillance strategies in pandemic settings.
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OBJECTIVES@#Many countries have authorized the emergency use of oral antiviral agents for patients with mild-to-moderate cases of coronavirus disease 2019 (COVID-19). We assessed the cost-effectiveness of these agents for reducing the number of severe COVID-19 cases and the burden on Korea’s medical system. @*METHODS@#Using an existing model, we estimated the number of people who would require hospital/intensive care unit (ICU) admission in Korea in 2022. The treatment scenarios included (1) all adult patients, (2) elderly patients only, and (3) adult patients with underlying diseases only, compared to standard care. Based on the current health system capacity, we calculated the incremental costs per severe case averted and hospital admission for each scenario. @*RESULTS@#We estimated that 236,510 COVID-19 patients would require hospital/ICU admission in 2022 with standard care only. Nirmatrelvir/ritonavir (87% efficacy) was predicted to reduce this number by 80%, 24%, and 17% when targeting all adults, adults with underlying diseases, and elderly patients (25, 8, and 4%, respectively, for molnupiravir, with 30% efficacy). Nirmatrelvir/ritonavir use is likely to be cost-effective, with predicted costs of US$8,878, US$8,964, and US$1,454, per severe patient averted for the target groups listed above, respectively, while molnupiravir is likely to be less cost-effective, with costs of US$28,492, US$29,575, and US$7,915, respectively. @*CONCLUSIONS@#In Korea, oral treatment using nirmatrelvir/ritonavir for symptomatic COVID-19 patients targeting elderly patients would be highly cost-effective and would substantially reduce the demand for hospital admission to below the capacity of the health system if targeted to all adult patients instead of standard care.
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Purpose@#Real-world experience with tocilizumab in combination with dexamethasone in patients with severe coronavirus disease (COVID-19) needs to be investigated. @*Materials and Methods@#A retrospective cohort study was conducted to evaluate the effect of severity-adjusted dosing of dexamethasone in combination with tocilizumab for severe COVID-19 from August 2020 to August 2021. The primary endpoint was 30-day clinical recovery, which was defined as no oxygen requirement or referral after recovery. @*Results@#A total of 66 patients were evaluated, including 33 patients in the dexamethasone (Dexa) group and 33 patients in the dexamethasone plus tocilizumab (DexaToci) group. The DexaToci group showed a statistically significant benefit in 30-day clinical recovery, compared to the Dexa group (p=0.024). In multivariable analyses, peak FiO2 within 3 days and tocilizumab combination were consistently significant for 30-day recovery (all p<0.05). The DexaToci group showed a significantly steeper decrease in FiO2 (-4.2±2.6) than the Dexa group (−2.7±2.6; p=0.021) by hospital day 15. The duration of oxygen requirement was significantly shorter in the DexaToci group than the Dexa group (median, 10.0 days vs. 17.0 days; p=0.006). Infectious complications and cellular and humoral immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the convalescence stage were not different between the two groups. @*Conclusion@#A combination of severity-adjusted dexamethasone and tocilizumab for the treatment of severe COVID-19 improved clinical recovery without increasing infectious complications or hindering the immune response against SARS-CoV-2.
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We used the nationwide claims database to calculate the incidence of thrombotic events and predict their overall 2-week incidence. From 2006 to 2020, the incidence of deep vein thrombosis (DVT), pulmonary embolism (PE), and disseminated intravascular coagulation (DIC) tended to increase. Unlike intracranial venous thrombosis (ICVT) and intracranial thrombophlebitis (ICTP), which showed no age difference, other venous embolism, and thrombosis (OVET), DIC, DVT, and PE were significantly more common in over 65 years.The overall 2-week incidence of ICVT was 0.21/1,000,000 (95% confidence interval [CI], 0.11–0.32). ICTP, OVET, DIC, DVT and PE were expected to occur in 0.08 (95% CI, 0.02– 0.14), 7.66 (95% CI, 6.08–9.23), 5.95 (95% CI, 4.88–7.03), 13.28 (95% CI, 11.92–14.64), 14.09 (95% CI, 12.80–15.37) per 1,000,000, respectively. To date, of 8,548,231 patients vaccinated with ChAdOx1 nCoV-19 in Korea, two had confirmed thrombosis with thrombocytopenia syndrome within 2 weeks. The observed incidence of ICVT after vaccination was 0.23/1,000,000.
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Background@#Vaccines against coronavirus disease 2019 (COVID-19) are raising concerns about vaccine safety, particularly in the context of large-scale immunization. To address public concerns, we measured the baseline incidence rates of major conditions potentially related to vaccine-related adverse events (VAEs). We aimed to provide a basis for evaluating VAEs and verifying causality. @*Methods@#Conditions of interest were selected from the US Vaccine Adverse Event Reporting System Table of Reportable Events and a recent report from a European consortium on vaccine surveillance. We used the National Health Insurance Service database in Korea to identify the monthly numbers of cases with these conditions. Data from January 2006 to June 2020 were included. Prediction models were constructed from the observed incidences using an autoregressive integrated moving average. We predicted the incidences of the conditions and their respective 95% confidence intervals (CIs) for January through December 2021. In addition, subgroup analysis for the expected vaccination population was conducted. @*Results@#Mean values (95% CIs) of the predicted monthly incidence of vasovagal syncope, anaphylaxis, brachial neuritis, acute disseminated encephalomyelitis, Bell's palsy, Guillain-Barré syndrome, encephalopathy, optic neuritis, transverse myelitis, immune thrombocytopenic purpura, and systemic lupus erythematosus in 2021 were 23.89 (19.81– 27.98), 4.72 (3.83–5.61), 57.62 (51.37–63.88), 0.03 (0.01–0.04), 8.58 (7.90–9.26), 0.26 (0.18– 0.34), 2.13 (1.42–2.83), 1.65 (1.17–2.13), 0.19 (0.14–0.25), 0.75 (0.61–0.90), and 3.40 (2.79– 4.01) cases per 100,000 respectively. The majority of the conditions showed an increasing trend with seasonal variations in their incidences. @*Conclusion@#We measured the incidence of a total of 11 conditions that could potentially be associated with VAEs to predict the monthly incidence in 2021. In Korea, conditions that could potentially be related to VAEs occur on a regular basis, and an increasing trend is observed with seasonality.
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Although obesity is a risk factor for infection, whether it has the same effect on coronavirus disease 2019 (COVID-19) need confirming. We conducted a retrospective propensity score matched case-control study to examine the association between obesity and COVID-19. This study included data from the Nationwide COVID-19 Registry and the Biennial Health Checkup database, until May 30, 2020. We identified 2,231 patients with confirmed COVID-19 and 10-fold-matched negative test controls. Overweight (body mass index [BMI] 23 to 24.9 kg/m2; adjusted odds ratio [aOR], 1.16; 95% confidence interval [CI], 1.1.03 to 1.30) and class 1 obesity (BMI 25 to 29.9 kg/m2; aOR, 1.27; 95% CI, 1.14 to 1.42) had significantly increased COVID-19 risk, while classes 2 and 3 obesity (BMI ≥30 kg/m2) showed similar but non-significant trend. Females and those <50 years had more robust association pattern. Overweight and obesity are possible risk factors of COVID-19.
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We used the nationwide claims database to calculate the incidence of thrombotic events and predict their overall 2-week incidence. From 2006 to 2020, the incidence of deep vein thrombosis (DVT), pulmonary embolism (PE), and disseminated intravascular coagulation (DIC) tended to increase. Unlike intracranial venous thrombosis (ICVT) and intracranial thrombophlebitis (ICTP), which showed no age difference, other venous embolism, and thrombosis (OVET), DIC, DVT, and PE were significantly more common in over 65 years.The overall 2-week incidence of ICVT was 0.21/1,000,000 (95% confidence interval [CI], 0.11–0.32). ICTP, OVET, DIC, DVT and PE were expected to occur in 0.08 (95% CI, 0.02– 0.14), 7.66 (95% CI, 6.08–9.23), 5.95 (95% CI, 4.88–7.03), 13.28 (95% CI, 11.92–14.64), 14.09 (95% CI, 12.80–15.37) per 1,000,000, respectively. To date, of 8,548,231 patients vaccinated with ChAdOx1 nCoV-19 in Korea, two had confirmed thrombosis with thrombocytopenia syndrome within 2 weeks. The observed incidence of ICVT after vaccination was 0.23/1,000,000.
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Background@#Vaccines against coronavirus disease 2019 (COVID-19) are raising concerns about vaccine safety, particularly in the context of large-scale immunization. To address public concerns, we measured the baseline incidence rates of major conditions potentially related to vaccine-related adverse events (VAEs). We aimed to provide a basis for evaluating VAEs and verifying causality. @*Methods@#Conditions of interest were selected from the US Vaccine Adverse Event Reporting System Table of Reportable Events and a recent report from a European consortium on vaccine surveillance. We used the National Health Insurance Service database in Korea to identify the monthly numbers of cases with these conditions. Data from January 2006 to June 2020 were included. Prediction models were constructed from the observed incidences using an autoregressive integrated moving average. We predicted the incidences of the conditions and their respective 95% confidence intervals (CIs) for January through December 2021. In addition, subgroup analysis for the expected vaccination population was conducted. @*Results@#Mean values (95% CIs) of the predicted monthly incidence of vasovagal syncope, anaphylaxis, brachial neuritis, acute disseminated encephalomyelitis, Bell's palsy, Guillain-Barré syndrome, encephalopathy, optic neuritis, transverse myelitis, immune thrombocytopenic purpura, and systemic lupus erythematosus in 2021 were 23.89 (19.81– 27.98), 4.72 (3.83–5.61), 57.62 (51.37–63.88), 0.03 (0.01–0.04), 8.58 (7.90–9.26), 0.26 (0.18– 0.34), 2.13 (1.42–2.83), 1.65 (1.17–2.13), 0.19 (0.14–0.25), 0.75 (0.61–0.90), and 3.40 (2.79– 4.01) cases per 100,000 respectively. The majority of the conditions showed an increasing trend with seasonal variations in their incidences. @*Conclusion@#We measured the incidence of a total of 11 conditions that could potentially be associated with VAEs to predict the monthly incidence in 2021. In Korea, conditions that could potentially be related to VAEs occur on a regular basis, and an increasing trend is observed with seasonality.
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Neutralizing antibodies targeted at the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have been developed and now under evaluation in clinical trials. The US Food and Drug Administration currently issued emergency use authorizations for neutralizing monoclonal antibodies in non-hospitalized patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at high risk for progressing to severe disease and/or hospitalization. In terms of this situation, there is an urgent need to investigate the clinical aspects and to develop strategies to deploy them effectively in clinical practice. Here we provide guidance for the use of anti-SARS-CoV-2 monoclonal antibodies for the treatment of COVID-19 based on the latest evidence.
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Despite the global effort to mitigate the spread, coronavirus disease 2019 (COVID-19) has become a pandemic that took more than 2 million lives. There are numerous ongoing clinical studies aiming to find treatment options and many are being published daily. Some effective treatment options, albeit of variable efficacy, have been discovered. Therefore, it is necessary to develop an evidence-based methodology, to continuously check for new evidence, and to update recommendations accordingly. Here we provide guidelines on pharmaceutical treatment for COVID-19 based on the latest evidence.
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Neutralizing antibodies targeted at the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have been developed and now under evaluation in clinical trials. The US Food and Drug Administration currently issued emergency use authorizations for neutralizing monoclonal antibodies in non-hospitalized patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at high risk for progressing to severe disease and/or hospitalization. In terms of this situation, there is an urgent need to investigate the clinical aspects and to develop strategies to deploy them effectively in clinical practice. Here we provide guidance for the use of anti-SARS-CoV-2 monoclonal antibodies for the treatment of COVID-19 based on the latest evidence.
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Despite the global effort to mitigate the spread, coronavirus disease 2019 (COVID-19) has become a pandemic that took more than 2 million lives. There are numerous ongoing clinical studies aiming to find treatment options and many are being published daily. Some effective treatment options, albeit of variable efficacy, have been discovered. Therefore, it is necessary to develop an evidence-based methodology, to continuously check for new evidence, and to update recommendations accordingly. Here we provide guidelines on pharmaceutical treatment for COVID-19 based on the latest evidence.
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Since the first case was reported in Wuhan, Hubei Province, China on December 12, 2019, Coronavirus disease 2019 (COVID-19) has spread widely to other countries since January 2020. As of April 16, 2020, 10635 confirmed cases have been reported, with 230 deaths in Korea. COVID-19 patients may be asymptomatic or show various clinical manifestations, including acute symptoms such as fever, fatigue, sore throat; pneumonia presenting as acute respiratory distress syndrome; and multiple organ failure. As COVID-19 has such varied clinical manifestations and case fatality rates, no standard antiviral therapy regimen has been established other than supportive therapy. In the present guideline, we aim to introduce potentially helpful antiviral and other drug therapies based on in vivo and in vitro research and clinical experiences from many countries.
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Background@#Cancer patients can be at a higher risk of infection due to drug-resistant bacteria than the general population for various reasons. We performed a retrospective study to evaluate possible risk factors and outcomes of extended-spectrum beta-lactamaseproducing Klebsiella pneumoniae (ESBL-KP) bacteremia in cancer patients. @*Materials and Methods@#Cases were divided into two groups based on whether or not the isolated strain produced ESBL and multivariable regressions were done to identify possible risk factors of ESBL-KP bacteremia and mortality. For ESBL-producing strain, additional molecular analysis was done. @*Results@#278 cases with KP bacteremia were identified between 2010 and 2012, of which ESBLproducers were 50 (18%). The presence of percutaneous drainage catheter [odds ratio (OR) 4.99, P <0.001] and prior exposure to certain classes of antibiotics including third-generation cephalosporin (OR 2.14, P = 0.03) had significant associations with ESBL-KP bacteremia. Individuals who died within 14 days after the onset of KP bacteremia were more likely to have higher mean Pitt bacteremia score (1.56 in survival group vs. 3.43 in mortality group, P <0.001), hemodialysis (OR 17.03, P = 0.01) and chronic liver disease (OR 5.57, P = 0.01). Although 14-day mortality was higher with ESBL production (OR 2.76, P = 0.04), no significant differences in 30-day mortality (OR 1.67, P = 0.20) and other morbidity indices were observed. 49 ESBL-KP isolates, 65.4% of them produced CTX-M-14 and CTX-M-15 enzymes, and ST711 was the most common. @*Conclusion@#There were several differences in clinical characteristics between ESBL-KP and nonESBL-KP bacteremia in cancer patients, similar to previous reports including non-cancer patients.
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Coronavirus disease 2019 (COVID-19) outbreak is spreading rapidly all over the world, being a major threat to public health. Since clinical feature of COVID-19 has not been fully evaluated yet, empirical antibacterial agents are frequently combined for the treatment of COVID-19 in addition to antiviral agents, concerning co-existing bacterial pathogens. We experienced a case of severe thrombocytopenia with epistaxis and petechiae, while treating a COVID-19 patient with ceftriaxone, levofloxacin, and lopinavir/ritonavir. The platelet count decreased to 2,000/mm 3 and recovered after discontinuation of the three suspected drugs. In treating a potentially fatal emerging infectious disease, empirical and/or experimental approach would be unavoidable. However, the present case suggests that the possibility of adverse effects caused by polypharmacy should also be carefully considered.